ArticlePloS one2011
Methylated HBHA produced in M. smegmatis discriminates between active and non-active tuberculosis disease among RD1-responders.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Pooled it
- A Systematic Review on NovelFrontiers in immunology · 2018Pooled it
- Two-HitFrontiers in immunology · 2019Trial
- C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay.Frontiers in immunology · 2024Observational
- Commercially available CD4 + and CD8 + IFN-γ release assays combined with an HBHA-induced IGRA improve the characterization of the tuberculosis spectrum and monitoring of treatment in children.European journal of pediatrics · 2023Article
- Analysis of a Combined HBHA and ESAT-6-Interferon-γ-Release Assay for the Diagnosis of Tuberculous Lymphadenopathies.Journal of clinical medicine · 2023Article
- Alternative biomarkers of tuberculosis infection in patients with immune-mediated inflammatory diseases.Frontiers in medicine · 2023Article
- Optimal Detection of Latent Mycobacterium tuberculosis Infection by Combined Heparin-Binding Hemagglutinin (HBHA) and Early Secreted Antigenic Target 6 (ESAT-6) Whole-Blood Interferon Gamma Release Assays.Journal of clinical microbiology · 2022Article
- In-Depth Immunophenotyping With Mass Cytometry During TB Treatment Reveals New T-Cell Subsets Associated With Culture Conversion.Frontiers in immunology · 2022Article
- Opti-4TB: A protocol for a prospective cohort study evaluating the performance of new biomarkers for active tuberculosis outcome prediction.Frontiers in medicine · 2022Article
- Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring.Scientific reports · 2021Article
- Early diagnosis of miliary tuberculosis in a hemodialysis patient by combining two interferon-γ-release assays: a case report.BMC nephrology · 2020Article
- Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance: A Multicentered Study.Frontiers in immunology · 2020Article
- Identification ofFrontiers in pediatrics · 2019Article
- Altered expression of antigen-specific memory and regulatory T-cell subsets differentiate latent and active tuberculosis.Immunology · 2018Article
- Immunogenicity of heparin-binding hemagglutinin expressed byIranian journal of basic medical sciences · 2018Article
- Immune characterization of the HBHA-specific response in Mycobacterium tuberculosis-infected patients with or without HIV infection.PloS one · 2017Article
- Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis.The European respiratory journal · 2016Review
- Added Value of Long-Term Cytokine Release Assays to Detect Mycobacterium tuberculosis Infection in HIV-Infected Subjects in Uganda.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Tuberculosis Biomarkers: From Diagnosis to Protection.Infectious disease reports · 2016Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA challenge in tuberculosis (TB) research is to develop a new immunological test that can help distinguish, among subjects responsive to QuantiFERON TB Gold In tube (QFT-IT), those who are able to control Mtb replication (remote LTBI, recent infection and past TB) from those who cannot (active TB disease). IFN-γ response to the Heparin-binding-hemagglutinin (HBHA) of Mtb has been associated with LTBI, but the cumbersome procedures of purifying the methylated and immunological active form of the protein from Mtb or M. bovis Bacillus Calmette et Guerin (BCG) have prevented its implementation in a diagnostic test. Therefore, the aim of the present study was to evaluate the IFN-γ response to methylated HBHA of Mtb produced in M. smegmatis (rHBHAms) in individuals at different stages of TB who scored positive to QFT-IT. METHODOLOGY/PRINCIPAL
findings87 individuals at different stages of TB who scored positive to QFT-IT were selected. IFN-γ response to in vitro whole blood stimulation with rHBHAms was evaluated by short-term and long-term tests and detected by ELISA or flow cytometry. We demonstrated that the IFN-γ response to rHBHAms is mediated by CD4(+) T-cells with an effector-memory phenotype. This response, evaluated by short-term-tests, is significantly lower in active TB than in remote LTBI (p = 0.0010) and past TB (p = 0.0152). These results were confirmed by long-term tests. The qualitative data confirmed that IFN-γ responses higher than the cut-off point identified by ROC analysis are associated with the status of non-active disease.
conclusionsIn this study we show that the T-cell response to a recombinant and methylated HBHA of Mtb produced in M. smegmatis is useful to discriminate between active and non-active TB disease among those responsive to QFT-IT in a whole blood system. Further studies are needed to improve the accuracy of the assay.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.